Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes
Authors: Lawrence J Appel, Morgan Grams, Mark Woodward, Katie Harris, Hisatomi Arima, John Chalmers, Hiroshi Yatsuya, Koji Tamakoshi, Yuanying Li, Josef Coresh, Yingying Sang, Kunihiro Matsushita, Kevan Polkinghorne, Steve Chadban, Adeera Levin, Ognjenka Djurdjev, Mila Tang, Luxia Zhang, Fang Wang, Jinwei Wang, Ming-Hui Zhao, Elke Schaeffner, Natalie Ebert, Nina Mielke, Marcello Tonelli, Anita Lloyd, Frank Sacks, Michael G Shlipak, Nisha Bansal, Mark Sarnak, Kazumasa Yamagishi, Isao Muraki, Yuji Shimizu, Hiroyasu Iso, Masafumi Fukagawa, Shoichi Maruyama, Takayuki Hamano, Naohiko Fujii, Takahiro Imaizumi, Natalia Alencar De Pinho, Marie Metzger, Bénédicte Stengel, Aghilès Hamroun, Ziad Massy, Tazeen H Jafar, Imtiaz Jehan, Juanita Hatcher, Nish Chaturvedi, Neil Poulter, David C Wheeler, Martin Landray, Amanda Anderson, Jing Chen, James Lash, Jon Taliercio, Peter (Wei) Yang, Katherine Tuttle, Radica Alicic, Susanne Nicholas, Jenny Shen, Ben Schöttker, Hannah Stocker, Dietrich Rothenbacher, Hermann Brenner, Daniel Levy, Shih-Jen Hwang, Markus P Schneider, Anna Köttgen, Heike Meiselbach, Kai-Uwe Eckardt, Alexander R Chang, Jamie A Green, H Lester Kirchner, Gurmukteshwar Singh, Simon Sawhney, Corri Black, Katie Wilde, Angharad Marks, Samira Bell, Moneeza Siddiqui, Colin Palmer, Ewan Pearson, Mariko Miyazaki, Masaaki Nakayama, Tae Yamamoto, Gen Yamada, Sadayoshi Ito, Massimo Cirillo, Angela Yee-Moon Wang, Henry Hon-Lin Wu, Hoi Ching Cheung, Victoria Ngai, Tang Ka Tak, Amit X Garg, Eric McArthur, Ann Young, Vivekanand Jha, Ashok Kumar Yadav, Vivek Kumar, April P Carson, Bessie A Young, Clarissa Diamantidis, Yuan-I Min, Tanjala S Purnell, Shizukiyo Ishikawa, Makiko Mieno, Kunihiro Yamagata, Kunitoshi Iseki, Koichi Asahi, Tsuneo Konta, Brian J Lee, Nigel J Brunskill, Laura Gray, Rupert Major, James Medcalf, Gabriel Chodick, Cheli Melzer Cohen, Jack FM Wetzels, Peter J Blankestijn, Arjan D van Zuilen, Lesley A Inker, Andrew S Levey, Joachim Ix, Ian de Boer, Ronit Katz, Florian Kronenberg, Barbara Kollerits, Eberhard Ritz, Dorothea Nitsch, Girish N Nadkarni, Lili Chan, Erwin P Bottinger, Wonsuk Oh, Zhihong Liu, Haitao Zhang, Lihua Zhang, Jose M Valdivielso, Marcelino Bermudez-Lopez, Milica Bozic, Maite Caus, Juan Miguel Diaz-Tocados, Benedicte Stengel, Katsuyuki Miura, Hirotsugu Ueshima, Akira Okayama, Aya Kadota, Tomonori Okamura, Laura Sola, Alejandro Ferreiro, Jose Santiago, Pablo Rios, Liliana Gadola , Ricardo  Silvariño, Takayoshi Ohkubo, Michihiro Satoh, Hirohito Metoki, Masahiro Kikuya, Elizabeth Ciemins, Jeff Mohl, Robert G Nelson, Robert L Hanson, Helen C Looker, Ron T Gansevoort, Lyanne M Kieneker, Stephan JL Bakker, Olivier Moranne, Cecile Couchoud, David Shepherd, Simerjot K Jassal, Jaclyn Bergstrom, Csaba P Kovesdy, Keiichi Sumida, Prabin Shrestha, Orlando Gutierrez, Katharine Cheung, Paul Muntner, Titi Ilori, Michelle Pena, Hiddo JL Heerspink, Edouard L Fu, Carl-Gustaf Elinder, Peter Barany, Juan J Carrero, Marie Evans, Charumathi Sabanayagam, Ching-Yu Cheng, Tien Yin Wong, Crystal Chong Chun Yuen, William Herrington, Natalie Staplin, Martin J Landray, Colin Baigent, Philip Kalra, Rajkumar Chinnadurai, Darren Green, Smeeta Sinha, James Ritchie, Frank LJ Visseren, Pascal Burger, Marielle Emmelot, Berend van Welzen, Oommen John, Balaji Gummidi, Arpita Ghosh, David Naimark, Navdeep Tangri, Chi-Pang Wen, Min-Kuang Tsai, Yoshiyuki Ueno, Masafumi Watanabe, Kazunobu Ichikawa, Mohammadhassan Mirbolouk, Fereidoun Azizi, Farzad Hadaegh, Farhad Hosseinpanah, Wen Shi, Dan Arking, Johan Ärnlöv, Anders Larsson, Vilmantas Giedraitis, Patrick Mark, Jamie Traynor, Michael Sullivan, Jennifer Lees, Jae won Yang, Jae il Shin, Jun young Lee, Jae seok Kim, Henk JG Bilo, Peter van Dijk, Mireille Edens, Joep Dille, Shoshana H Ballew, Juan-Jesus Carrero, Morgan E Grams, Jingsha Chen, Aditya Surapaneni, Morgan E. Grams, Josef Coresh, Kunihiro Matsushita, Shoshana H. Ballew, Yingying Sang, Aditya Surapaneni, Natalia Alencar de Pinho, Amanda Anderson, Lawrence J. Appel, Johan Ärnlöv, Fereidoun Azizi, Nisha Bansal, Samira Bell, Henk J. G. Bilo, Nigel J. Brunskill, Juan J. Carrero, Steve Chadban, John Chalmers, Jing Chen, Elizabeth Ciemins, Massimo Cirillo, Natalie Ebert, Marie Evans, Alejandro Ferreiro, Edouard L. Fu, Masafumi Fukagawa, Jamie A. Green, Orlando M. Gutierrez, William G. Herrington, Shih-Jen Hwang, Lesley A. Inker, Kunitoshi Iseki, Tazeen Jafar, Simerjot K. Jassal, Vivekanand Jha, Aya Kadota, Ronit Katz, Anna Köttgen, Tsuneo Konta, Florian Kronenberg, Brian J. Lee, Jennifer Lees, Adeera Levin, Helen C. Looker, Rupert Major, Cheli Melzer Cohen, Makiko Mieno, Mariko Miyazaki, Olivier Moranne, Isao Muraki, David Naimark, Dorothea Nitsch, Wonsuk Oh, Michelle Pena, Tanjala S. Purnell, Charumathi Sabanayagam, Michihiro Satoh, Simon Sawhney, Elke Schaeffner, Ben Schöttker, Jenny I. Shen, Michael G. Shlipak, Smeeta Sinha, Benedicte Stengel, Keiichi Sumida, Marcello Tonelli, Jose M. Valdivielso, Arjan D. van Zuilen, Frank L. J. Visseren, Angela Yee-Moon Wang, Chi-Pang Wen, David C. Wheeler, Hiroshi Yatsuya, Kunihiro Yamagata, Jae won Yang, Ann Young, Haitao Zhang, Luxia Zhang, Andrew S. Levey, Ron T. Gansevoort
Journal: JAMA (2023)

Importance Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. Objective To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Design, Setting, and Participants Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. Exposures The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). Main Outcomes and Measures The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Results Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m 2 (SD, 22 mL/min/1.73 m 2 ) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m 2 (SD, 22 mL/min/1.73 m 2 ) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m 2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m 2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). Conclusions and Relevance In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.